Literature: Wang W, Yang N, Wang L, Zhu Y, Chu X, Xu W, Li Y, Xu Y, Gao L, Zhang B, Zhang G, Sun Q, Wang W, Wang Q, Zhang W, Chen D the tet-sall4-bmp regulatory axis controls craniofacial cartilage development. cell rep. 2024 feb 29;43(3):113873. doi: 10.1016/j.celrep.2024.113873. epub ahead of print. pmid: 38427557.
Magazine: Cell Reports
Impact factor: 88
Craniofacial microsomia (CFM) is a general term for various craniofacial deformities, including structural abnormalities of the craniofacial bones (lower jaw, maxilla, ears, and orbits), facial nerves, and facial soft tissues. CFM is a congenital defect that is usually caused by abnormal development of the pharyngeal arch in the embryo. However, the molecular basis of the pathogenesis of CFM is largely unknown.
The zebrafish model was used to investigate the pathogenesis of CFM. In early embryos, TET2 and TET3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing showed that deletion of TET2 3 impaired chondrocyte differentiation due to insufficient BMP signaling. In addition, biochemical and genetic evidence suggests that sequence-specific 5MC5HMC-binding protein SALL4 binds to the promoter of BMP4, activates BMP4 expression, and controls pharyngeal chondrage. Mechanistically, SALL4 guides the co-phase separation of TET2 3 and SALL4 to form a condensate, which mediates the oxidation of 5MC on the BMP4 promoter, thereby promoting BMP4 expression and achieving sufficient BMP signaling. These findings suggest that the Tet-BMP-SALL4 regulatory axis is essential for pharyngeal cartilage development.
Overall, the study provides insights into the understanding of craniofacial development and the pathogenesis of CFM. Hotspot Engine Program